Benzodiazepines, high-efficacy, non-subtype selective GABAA positive modulators, are fast-onset anxiolytics with a number of side effects, such as sedation, motor incoordination, abuse liability, dependence, and memory impairment. Studies using point mutations introduced into the mouse genome (knock-in mutations) have suggested that GABAA/α2 subunit-containing receptors mediate anxiolytic effects and GABAA/α1 subunit-containing receptors mediate sedative/ataxic effects of classical benzodiazepines. In addition, GABAA/α1-selective compounds, such as zolpidem (Ambien®), are clinically used as sedative/hypnotics. Compounds with high intrinsic efficacy at the GABAA/α2 receptors and reduced intrinsic efficacy at the GABAA/α1 receptors show reduced potential for motoric side effects and possibly reduced abuse liability, while retaining anxiolytic-like activity in preclinical models. Thus, a compound with functional selectivity for the GABAA/α2 receptors has the potential to be a non-sedating anxiolytic.